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Challenges of the Unknown: Clinical Application of Microbial Metagenomics

机译:未知的挑战:微生物基因组学的临床应用

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Availability of fast, high throughput and low cost whole genome sequencing holds great promise within public health microbiology, with applications ranging from outbreak detection and tracking transmission events to understanding the role played by microbial communities in health and disease. Within clinical metagenomics, identifying microorganisms from a complex and host enriched background remains a central computational challenge. As proof of principle, we sequenced two metagenomic samples, a known viral mixture of 25 human pathogens and an unknown complex biological model using benchtop technology. The datasets were then analysed using a bioinformatic pipeline developed around recent fast classification methods. A targeted approach was able to detect 20 of the viruses against a background of host contamination from multiple sources and bacterial contamination. An alternative untargeted identification method was highly correlated with these classifications, and over 1,600 species were identified when applied to the complex biological model, including several species captured at over 50% genome coverage. In summary, this study demonstrates the great potential of applying metagenomics within the clinical laboratory setting and that this can be achieved using infrastructure available to nondedicated sequencing centres.
机译:快速,高通量和低成本的全基因组测序的可用性在公共卫生微生物学中具有广阔的前景,其应用范围从爆发检测和追踪传播事件到了解微生物群落在健康和疾病中的作用。在临床宏基因组学中,从复杂且宿主丰富的背景中鉴定微生物仍然是计算的主要挑战。作为原理证明,我们使用台式技术对两个宏基因组学样本,已知的25种人类病原体的病毒混合物和未知的复杂生物学模型进行了测序。然后使用围绕最新快速分类方法开发的生物信息流水线对数据集进行分析。在多种来源的宿主污染和细菌污染的背景下,一种有针对性的方法能够检测出20种病毒。另一种非靶向的鉴定方法与这些分类高度相关,当应用于复杂的生物模型时,鉴定出了1,600多种,包括以50%以上的基因组覆盖率捕获的几种。总而言之,这项研究证明了在临床实验室环境中应用宏基因组学的巨大潜力,并且可以使用非专用测序中心可用的基础设施来实现这一目标。

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